In animal lungs, there occurs a physiologically active substance, called pulmonary surfactant, which is mainly composed of phospholipids. The pulmonary surfactant is mostly biosynthesized in, and secreted from, type-II epithelial cells of the alveoli and exists not only in the alveolar region but also in the entire airway covering its internal wall. This substance is known to prevent collapse of the alveoli by reducing the surface tension and this is an important physiological function for the maintenance of respiratory function. Infant respiratory distress syndrome which may lead to acute respiratory failure occurs from a deficiency in pulmonary surfactant. Many reports indicate that such decrease or dysfunction of pulmonary surfactant is also found in adult respiratory distress syndrome. Hallman, et al. reported that an abnormality of pulmonary surfactant may occur also in chronic respiratory failure (Journal of Clinical Investigation, 70, 673-683, 1982).
Pulmonary surfactant plays an important role as a mechanism of defense in the whole respiratory tract, in addition to its anti-collapse action. Thus, its preventive effect against pulmonary edema, against the infection by bacteria and viruses, and against polluted atmosphere and antigens which might induce respiratory tract inflammation and asthmatic attacks has been described in many reports. In addition, pulmonary surfactant is known to be playing an important role in the removal of foreign matter from the airway by lubricating the respiratory tract lumen and activating mucociliary transport.
These multiple physiological functions which pulmonary surfactant is discharging in the respiratory system suggest that its qualitative change and quantitative reduction are associated with the onset and exacerbation of many respiratory diseases. Therefore, promoting the secretion of pulmonary surfactant will probably make it possible to treat or prevent various respiratory diseases, such as acute respiratory failure (e.g., infant or adult respiratory distress syndrome), acute and chronic bronchitis, infectious diseases, asthma and chronic respiratory failure.
It is also likely that administration of pulmonary surfactant to a pregnant woman who has a potential to be delivered of a premature child will prevent the incidence of infant respiratory distress syndrome.
Heretofore, attempts have been made to utilize the natural or a recombinant pulmonary surfactant as it is or a composition containing the same (JP-B-1-13690, the term "JP-B" as used herein means an "examined Japanese patent publication", JP-A(PCT)-63-501792 and JP-A-2-53798, the term "JP-A" as used herein means an "unexamined published Japanese patent application"). However, only ambroxol, which is commercially available as an expectorant (Merck Index 11, pp. 62-63, 392, Ambroxol), may be reckoned as the substance that has ever been found to have the activity to promote the secretion of pulmonary surfactant (Post. et al.: Lung, 161, 349-359, 1983).
Meanwhile, among tri(lower alkoxy)benzene derivatives, a trimethoxybenzene substituted by a group of the formula: ##STR3## is disclosed in Journal of Medicinal Chemistry, 9, 631, 1966 as a compound having antihistaminic activity. JP-A-62-240653 discloses a compound of the following formula as an antianginal agent. ##STR4## wherein R.sub.1 and R.sub.4 independently represent a phenyl group which may optionally be substituted by 1, 2 or 3 members of halogen, trifluoromethyl, C.sub.1-4 alkoxy, C.sub.1-4 alkyl, cyano, hydroxy, nitro, NR.sub.5 R.sub.6 and O.sub.2 SNR.sub.5 --R.sub.6 (where R.sub.5 and R.sub.6 independently represent hydrogen or C.sub.1-6 alkyl, or jointly represent C.sub.3-6 polymethylene) or a phenyl group which may be di-substituted by C.sub.1-2 alkylenedioxy in the adjacent carbon positions and optionally by one member of said groups; R.sub.2 is selected from among (CH.sub.2).sub.2 CN (where z is 0 or an integer of 1 through 4), C.sub. alkyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl-C.sub.1-4 alkyl, phenyl-C.sub.1-4 alkyl, pyridyl, pyridyl-C.sub.1-4 alkyl, COR.sub.7, COCH.sub.2 COR.sub.7, SO.sub.2 R.sub.7, CO.sub.2 R.sub.7, CONHR.sub.7 and CSNHR.sub.7 (where R.sub.7 is selected from among C.sub.3-12 alkyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkyl-C.sub.1-4 alkyl, phenyl and phenyl-C.sub.1-4 alkyl and the optional alkyl moiety of R.sub.7 may optionally be substituted by hydroxy or C.sub.1-4 alkanoyloxy), the optional pyridyl or phenyl moiety of R.sub.2 may optionally be substituted as defined for R.sub.1 and R.sub.4 and the optional cycloalkyl moiety of R.sub.2 may optionally be substituted by 1 or 2 C.sub.1-4 alkyls; R.sub.3 represents hydrogen or C.sub.1-4 alkyl; A represents C.sub.2-6 alkylene; and B represents C.sub.1-4 alkylene.
However, the above literature neither disclose nor suggest that any tri(lower alkoxy)benzene derivative ever promotes secretion of pulmonary surfactant.